ethyl 1-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate | 256664-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 1-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate
• 英文别名: 1-(2-ethoxycarbonyl-ethyl)-indole-2-carboxylic acid ethyl ester；1-(2-Aethoxycarbonyl-aethyl)-indol-2-carbonsaeure-aethylester；Ethyl 2-(ethoxycarbonyl)-1H-indole-1-propanoate；ethyl 1-(3-ethoxy-3-oxopropyl)indole-2-carboxylate
• CAS: 256664-26-3
• 化学式: C₁₆H₁₉NO₄
• 分子量: 289.331
• InChiKey: RVIZLENOFZAKEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate 在 甲醇 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以to give the title compound as a colorless oil in 1.12 g (4.5 mmol)的产率得到ethyl 1-(3-hydroxypropyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS

  摘要：

  本发明提供了一种抑制抗凋亡Bcl-2家族成员髓系细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了制药组合物以及使用化合物治疗因Mcl-1蛋白过度表达或失调而表现出的疾病和症状（例如癌症）的方法。

  公开号：

  US20150336925A1
• 作为产物：
  描述：

  1-(2-carboxyethyl)-1H-indole-2-carboxylic acid 在 盐酸 作用下， 生成 ethyl 1-(3-ethoxy-3-oxopropyl)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Lukes; Blaha, Collection of Czechoslovak Chemical Communications, 1957, vol. 22, p. 626

  摘要：

  DOI：

文献信息

• Synthesis and Biological Activity of N-(Aminoiminomethyl)-1H-indole Carboxamide Derivatives as Na+/H+ Exchanger Inhibitors.
  作者：Masafumi KITANO、Atsuyuki KOJIMA、Kazuhiro NAKANO、Akira MIYAGISHI、Tsuyoshi NOGUCHI、Naohito OHASHI

  DOI：10.1248/cpb.47.1538

  日期：——

  N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7-position of the indole ring system showed that a substitution at the 2-position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series

  合成了一系列的N-（氨基亚氨基甲基）-1H-吲哚羧酰胺衍生物，并测定了它们对Na + / H +交换剂的抑制能力。吲哚环系统2到7位羰基胍基团的变化表明，在2位取代可以最有效地提高Na + / H +交换子的抑制活性。这导致合成和评估了一系列广泛的N-（氨基亚氨基甲基）-1H-吲哚-2-羧酰胺衍生物。在吲哚环系统的1-位具有烷基或取代的烷基的衍生物显示出更高水平的体外活性。N-（氨基亚氨基甲基）-1-（2-苯乙基）-1H-吲哚-2-羧酰胺（49）具有最强的活性。
• Substituted benzofuran, benzothiophene and indole MCL-1 inhibitors
  申请人：VANDERBILT UNIVERSITY

  公开号：US10093640B2

  公开（公告）日：2018-10-09

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。
• Substituted benzofuran, benzothiophene and indole Mcl-1 inhibitors
  申请人：Vanderbilt University

  公开号：US10844032B2

  公开（公告）日：2020-11-24

  The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

  本发明提供了抑制抗凋亡 Bcl-2 家族成员骨髓细胞白血病-1（Mcl-1）蛋白活性的化合物。本发明还提供了药物组合物以及使用化合物治疗以 Mcl-1 蛋白过度表达或失调为特征的疾病和病症（如癌症）的方法。
• Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design
  作者：Anders Friberg、Dominico Vigil、Bin Zhao、R. Nathan Daniels、Jason P. Burke、Pedro M. Garcia-Barrantes、DeMarco Camper、Brian A. Chauder、Taekyu Lee、Edward T. Olejniczak、Stephen W. Fesik

  DOI：10.1021/jm301448p

  日期：2013.1.10

  Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family of proteins, is overexpressed and amplified in various cancers and promotes the aberrant survival of tumor cells that otherwise would undergo apoptosis. Here we describe the discovery of potent and selective Mcl-1 inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified two chemically distinct hit series that bind to different sites on Mcl-1. Members of the two fragment classes were merged together to produce lead compounds that bind to Mcl-1 with a dissociation constant of <100 nM with selectivity for Mcl-1 over Bcl-xL and Bcl-2. Structures of merged compounds when complexed to Mcl-1 were obtained by X-ray crystallography and provide detailed information about the molecular recognition of small-molecule ligands binding Mcl-1. The compounds represent starting points for the discovery of clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers.
• [EN] SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS<br/>[FR] INHIBITEURS DE LA MCL-1 À BASE DE BENZOFURANE, DE BENZOTHIOPHÈNE ET D'INDOLE SUBSTITUÉS
  申请人：UNIV VANDERBILT

  公开号：WO2014047427A3

  公开（公告）日：2015-07-16